rs6662617

chr1-56803848-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004303.5(FYB2):c.10-11045T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,054 control chromosomes in the GnomAD database, including 9,767 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9767 hom., cov: 32)
• Consequence: FYB2 NM_001004303.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610

Genes affected

FYB2 (HGNC:27295): (FYN binding protein 2) Involved in T cell receptor signaling pathway and cell adhesion mediated by integrin. Located in immunological synapse and membrane raft. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYB2	NM_001004303.5	c.10-11045T>C		intron_variant		ENST00000343433.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYB2	ENST00000343433.7	c.10-11045T>C		intron_variant		1	NM_001004303.5	P1
FYB2	ENST00000484327.1	n.416-11045T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51421 AN: 151936 Hom.: 9768 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.339

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.338 AC: 51422 AN: 152054 Hom.: 9767 Cov.: 32 AF XY: 0.332 AC XY: 24648 AN XY: 74306

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.339

Alfa AF: 0.415 Hom.: 18176

Bravo AF: 0.323

Asia WGS AF: 0.253 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.7
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6662617; hg19: chr1-57269521; COSMIC: COSV58583710;